| Mitochondrial complex II is essential for hypoxia-induced pulmonary vasoconstriction of intra- but not of pre-acinar arteries. | |
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MedLine Citation:
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PMID: 22215723 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims Alveolar hypoxia acutely elicits contraction of pulmonary arteries leading to rise in pulmonary arterial pressure (PAP) and shifting blood to better ventilated areas of the lung. The molecular mechanisms underlying this hypoxic pulmonary vasoconstriction (HPV) are still incompletely understood. Here, we investigated the role of succinate dehydrogenase (SDH; synonymous to mitochondrial complex II) in HPV with particular emphasis on regional differences along the vascular bed and consequences for PAP and perfusion-to-ventilation matching utilizing mutant mice heterozygous for the SDHD subunit of complex II (SDHD(+/-)).Methods and Results Western blots revealed reduced protein content of complex II subunits SDHA, -B, and -C in lungs of SDHD(+/-)mice, despite unaffected mRNA content as determined by real-time PCR. HPV of small (20-50 µm) intra-acinar and larger (51-100 µm) pre-acinar arteries was evaluated by videomorphometric analysis of precision-cut lung slices. The hypoxic response was detectable in pre-acinar, but absent from intra-acinar arteries of SDHD(+/-)mice. In isolated perfused lungs, basal PAP and its hypoxia-induced increase were indistinguishable between both mouse strains. Arterial oxygenation was measured after provocation of regional ventilatory failure by tracheal fluid instillation in anesthetized mice, and it declined more in SDHD(+/-) than in wild-type mice.Conclusions SDHD is required for the formation of a stable mitochondrial complex II and it is selectively important for HPV of intra-acinar vessels. This specialized vascular segment participates in perfusion-to-ventilation matching but does not significantly contribute to acute hypoxic rise in PAP which results from more proximal vasoconstriction. |
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Authors:
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Renate Paddenberg; Martina Tiefenbach; Petra Faulhammer; Anna Goldenberg; Barbara Gries; Uwe Pfeil; Katrin S Lips; José I Piruat; José López-Barneo; Ralph T Schermuly; Norbert Weissmann; Wolfgang Kummer |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-2 |
Journal Detail:
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Title: Cardiovascular research Volume: - ISSN: 1755-3245 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute of Anatomy and Cell Biology, ECCPS, Justus-Liebig-University, Giessen, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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